Pioglitazone Reduces Neointima Formation After Coronary Stent Implantation - Pioglitazone Reduces Neointima Formation After Coronary Stent Implantation

Description:

The goal of the study was to evaluate the effect on neointima formation of treatment with pioglitazone, an oral antidiabetic drug, compared with placebo in nondiabetic patients undergoing coronary stent implantation for de novo lesions.

Hypothesis:

Treatment with pioglitazone will be associated with a reduction in neointima formation compared with placebo in nondiabetic patients undergoing coronary stent implantation for de novo lesions.

Study Design

Study Design:

Patients Enrolled: 50
Mean Follow Up: Six months
Mean Patient Age: Mean age 62 years
Female: 27

Patient Populations:

Angina and/or exercise-induced ischemia, significant stenosis in a native coronary artery suitable for stenting, and age 25-80 years

Exclusions:

Diabetes, acute ST elevation myocardial infarction, systemic inflammation disease, or renal impairment

Primary Endpoints:

Neointima formation at six-month follow-up

Secondary Endpoints:

Angiographic stenosis

Drug/Procedures Used:

Nondiabetic patients were randomized after coronary stent implantation to either treatment with pioglitazone (30 mg/OD; n=25), an oral antidiabetic drug, or placebo (n=25) in addition to standard therapy. Intravascular ultrasound was performed at baseline and at six-month follow-up.

Principal Findings:

Baseline clinical and angiographic characteristics were similar between the two treatment groups. There were no differences in baseline fasting blood glucose (5.4 mmol/l for pioglitazone vs. 5.7 mmol/l for placebo), fasting insulin, HbA1c (5.7% for pioglitazone vs. 5.6% for placebo), or lipid levels. An average of 1.11 stents were used in the pioglitazone group and 1.15 for the placebo group.

There were no differences in change in fasting blood glucose, fasting insulin, HbA1c, or lipid levels. The primary endpoint of neointimal volume within the stented segment at six-month follow-up was significantly lower in the pioglitazone group compared with placebo (2.3 mm3/mm vs. 3.1 mm3/mm, p<0.05). Total plaque volume was also lower at follow-up in the pioglitazone group compared with placebo (11.2 mm3/mm vs. 13.2 mm3/mm, p<0.05).

Percent stenosis was lower in the pioglitazone group compared with placebo (22.1% vs. 37.3%, p=0.01). Minimum lumen diameter trended larger in the pioglitazone group (2.14 mm vs. 1.94 mm, p=0.29).

Interpretation:

Among nondiabetic patients undergoing coronary stent implantation for de novo lesions, treatment with the oral antidiabetic drug pioglitazone was associated with a reduction in neointima formation compared with placebo at six-month follow-up. Additionally, a notable reduction in stenosis was observed.

While provocative, the sample size of the trial was small (n=50) and larger trials will be needed to confirm these findings and to evaluate potential adverse events and whether improvements in these surrogate endpoints result in improvements in the need for target lesion revascularization. While drug-eluting stents have already been shown to be effective in reducing restenosis, therapies such as this one may be beneficial in patients who cannot be treated with drug-eluting stents, such as patients with diffuse disease or those with small arteries.

References:

Marx N, et al. Pioglitazone Reduces Neointima Formation After Coronary Stent Implantation. Circulation. 2005;112:2792-2798.

Presented by Dr. Nikolaus Marx at the March 2005 ACC Annual Scientific Session, Orlando, FL.

Clinical Topics: Invasive Cardiovascular Angiography and Intervention, Prevention, Atherosclerotic Disease (CAD/PAD), Interventions and Coronary Artery Disease, Diet

Keywords: Neointima, Coronary Artery Disease, Insulin, Follow-Up Studies, Biological Markers, Drug-Eluting Stents, Blood Glucose, Hypoglycemic Agents, Constriction, Pathologic, Fasting, Thiazolidinediones


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